Bifidobacterium breve MRx0004 protects against airway inflammation in a severe asthma model by suppressing both neutrophil and eosinophil lung infiltration

Emma J Raftis, Margaret I Delday, Philip Cowie, Seánín M McCluskey, Mark D Singh, Anna Ettorre, Imke E Mulder

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Abstract

Asthma is a phenotypically heterogeneous disease. In severe asthma, airway inflammation can be predominantly eosinophilic, neutrophilic, or mixed. Only a limited number of drug candidates are in development to address this unmet clinical need. Live biotherapeutics derived from the gut microbiota are a promising new therapeutic area. MRx0004 is a commensal Bifidobacterium breve strain isolated from the microbiota of a healthy human. The strain was tested prophylactically and therapeutically by oral gavage in a house dust mite mouse model of severe asthma. A strong reduction of neutrophil and eosinophil infiltration was observed in lung bronchoalveolar lavage fluid following MRx0004 treatment. Peribronchiolar and perivascular immunopathology was also reduced. MRx0004 increased lung CD4+CD44+ cells and CD4+FoxP3+ cells and decreased activated CD11b+ dendritic cells. Cytokine analysis of lung tissue revealed reductions of pro-inflammatory cytokines and chemokines involved in neutrophil migration. In comparison, anti-IL-17 antibody treatment effectively reduced neutrophilic infiltration and increased CD4+FoxP3+ cells, but it induced lung eosinophilia and did not decrease histopathology scores. We have demonstrated that MRx0004, a microbiota-derived bacterial strain, can reduce both neutrophilic and eosinophilic infiltration in a mouse model of severe asthma. This novel therapeutic is a promising next-generation drug for management of severe asthma.

Original languageEnglish
Article number12024
JournalScientific Reports
Volume8
DOIs
Publication statusPublished - 13 Aug 2018

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Eosinophils
Neutrophils
Asthma
Inflammation
Lung
Microbiota
Bronchoalveolar Lavage Fluid
Cytokines
Pyroglyphidae
Interleukin-17
Neutrophil Infiltration
Eosinophilia
Therapeutics
Chemokines
Pharmaceutical Preparations
Dendritic Cells
Bifidobacterium breve
Antibodies

Keywords

  • Journal Article

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Bifidobacterium breve MRx0004 protects against airway inflammation in a severe asthma model by suppressing both neutrophil and eosinophil lung infiltration. / Raftis, Emma J; Delday, Margaret I; Cowie, Philip; McCluskey, Seánín M; Singh, Mark D; Ettorre, Anna; Mulder, Imke E.

In: Scientific Reports, Vol. 8, 12024, 13.08.2018.

Research output: Contribution to journalArticle

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abstract = "Asthma is a phenotypically heterogeneous disease. In severe asthma, airway inflammation can be predominantly eosinophilic, neutrophilic, or mixed. Only a limited number of drug candidates are in development to address this unmet clinical need. Live biotherapeutics derived from the gut microbiota are a promising new therapeutic area. MRx0004 is a commensal Bifidobacterium breve strain isolated from the microbiota of a healthy human. The strain was tested prophylactically and therapeutically by oral gavage in a house dust mite mouse model of severe asthma. A strong reduction of neutrophil and eosinophil infiltration was observed in lung bronchoalveolar lavage fluid following MRx0004 treatment. Peribronchiolar and perivascular immunopathology was also reduced. MRx0004 increased lung CD4+CD44+ cells and CD4+FoxP3+ cells and decreased activated CD11b+ dendritic cells. Cytokine analysis of lung tissue revealed reductions of pro-inflammatory cytokines and chemokines involved in neutrophil migration. In comparison, anti-IL-17 antibody treatment effectively reduced neutrophilic infiltration and increased CD4+FoxP3+ cells, but it induced lung eosinophilia and did not decrease histopathology scores. We have demonstrated that MRx0004, a microbiota-derived bacterial strain, can reduce both neutrophilic and eosinophilic infiltration in a mouse model of severe asthma. This novel therapeutic is a promising next-generation drug for management of severe asthma.",
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